AB0494 ADIPOSITY SEEMS TO NOT INTERFERE WITH THE JAK INHIBITORS RESPONSE IN RHEUMATOID ARTHRITIS: AN EXPLORATORY STUDY
Authors: E. Tovar-Sugrañes, M. Andrés, V. Jovani, S. Gomez-Sabater, R. Caño-Alameda, P. Vela Casasempere
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Cumulative data show how an excess body weight may hamper the activity of some anti-rheumatic drugs in rheumatoid arthritis (RA), but we lack studies in this regard on the new JAK-kinase inhibitors (JAKinibs). <h3>Objectives</h3> To prospectively evaluate the impact of adiposity on the anti-inflammatory response of JAKinibs in RA. <h3>Methods</h3> Observational, prospective, single-center exploratory study. We sequentially included adult patients from tertiary center clinics, with a clinical diagnosis of RA and a new JAKinib prescription by their treating rheumatologists. Only JAKinibs-naïve patients were allowed. For this analysis, during the follow up, csDMARD was required to remain unchanged. Patients participating in weight loss or bariatric surgery programs were also excluded. We used three different definitions for <i>adiposity</i>: A) body mass index (BMI), as kg/m2; B) body fat percentage, measured by impedancemetry; and C) blood levels of LDL and HDL cholesterol and triglycerides. We defined dyslipidemia as total cholesterol &gt;200mg/dl and/or triglycerides &gt;150mg/dl at blood tests. The potential modulating effect of adiposity on the effectiveness of JAKinib therapy was assessed on the change of DAS28-CRP and DAS28-ESR between baseline and 3 months later (when the peak action of JAKinibs is theoretically met). ANOVA regression was used to compare changes in DAS28 CRP/ESR regarding adiposity variables. When significant associations were found, a multivariate linear regression model was built. Software R v.4.2.1 was used. <h3>Results</h3> From an initial sample of 20 patients, 4 were excluded from analysis (2 stopping JAKinib due to intolerance, 2 as the cDMARD dose was modified), which finally left 16 participants. Median age was 57years (IQR 50.75 to 65.5) and 75% were females. Four patients were bDMARD-naïve and 9 were on concurrent csDMARD. 75% (n=12) of the subjects received 4mg baricitinib daily, the remaining 4 cases received 15mg upadacitinib daily. Median BMI was 27.7kg/m<sup>2</sup> (IQR 26.25 to 31.38), being 31.5% thus obese. Median body fat percentage was 34.95% (31.38 to 40.55). Ten patients achieved the dyslipidemia cutoff, 75 % of whom received lipid lowering treatment. Patients had mostly moderate-high activity measured by DAS28 at baseline (81.25%), while after 3 months no patient was on high activity and 62.5% and 56.25% (CRP/ESR) showed low activity and remission, respectively. The results for the association analyses between adiposity and changes in DAS28-ESR are given in <b>Table 1</b>. No association was found neither for BMI or body fat percentage, while a positive, independent relation with triglycerides was noted (not with LDL o HDL). No adiposity variables were found associated with changes in DAS28-CRP. <h3>Conclusion</h3> No relevant impact of adiposity was noted on the anti-inflammatory effect of JAKinibs after three months of use in RA patients. Our findings support no dose adjustment for JAKinibs, independently of their weight or adiposity. This study should be replicated in larger studies to confirm our observations. <h3>Acknowledgements</h3> The realization of this study was possible thanks to the funding granted by ISABIAL. <h3>Disclosure of Interests</h3> Ernesto Tovar-Sugrañes Speakers bureau: UCB and Amgen, Mariano Andrés Speakers bureau: Lilly, Vega Jovani: None declared, Silvia Gomez-Sabater: None declared, Rocio Caño-Alameda: None declared, Paloma Vela Casasempere Speakers bureau: Pfizer, Lilly, Abbvie, Grant/research support from: Pfizer, Lilly, Abbvie.